Learning and memory are basic functions of the brain that are necessary for an animal to adapt to the environment. Elucidation of the neural mechanisms of learning/memory is one of the important issues in the field of neurobehavioral study/neurophysiology, and researches have been conducted to date in various animal species. Among them, insects have a high level of learning ability considering a relatively small number of nerve cells and a simple structure of the nervous system, and therefore they are a very useful material for studying learning/memory.
The present inventors have conducted studies of molecular mechanism of learning/memory by employing an olfactory associative learning system using Gryllus bimaculatus (hereinafter, referred to as a “cricket”) as a material and water as a reward stimulus. When adult crickets receive olfactory reward associative conditioning once by being given water in a thirsty state while smelling a certain smell (for example, peppermint), associative learning between the reward and the smell is established and they tend to favor that smell. This memory, however, is a short-term memory that is lost in a few hours. When the associative conditioning is conducted for three or more times at intervals, a long-term memory that persists for life can be formed. Similar to long-term memories in other animal species, long-term memories of crickets are dependent on protein synthesis. Moreover, a number of biological molecules that play an important role in formation of long-term memories in crickets have been identified, including nitrogen monoxide (NO), cGMP, cAMP, PKA and else, where many of them are also found to be important for the process of long-term memory formation in mice and rats. These substances, however, are not recognized to be effective in enhancing a memory when administered after the training. Searching for a substance that is capable of enhancing a memory not only before the training but even after the training appears to be beneficial in treating learning disorders and the like.
Recently, the present inventors found that formation of short-term memories is normal but formation of long-term memories is significantly deteriorated in aged crickets older than the average lifetime (age-related memory disorders). Age-related memory disorders have been recognized not only in rodents such as rats and mice, but also in invertebrates such as drosophila and nematodes. While there are various theories regarding the causes of age-related memory disorders, “active oxygen theory” is gaining broad acceptance, which suggests that active oxygen increasing with age gives damage to protein, DNA and else constituting the cells. Melatonin known as an antioxidant substance is believed to be effective for age-related memory disorders. For example, in the previous study by the present inventors, melatonin was mixed into a feed or water and given to mice, drosophila and crickets as experimental animals over a long period of time, by which age-related memory disorders were prevented (Name of Document: Japanese Patent No. 4993900). However, the mechanism of the age-related memory disorder has not yet been understood.